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Журнал "Гастроэнтерология" Том 56, №4, 2022

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Обмеження та значення неінвазивного тесту для оцінки хронічного захворювання печінки

Обмеження та значення неінвазивного тесту для оцінки хронічного захворювання печінки

Авторы: V. Siva Kesava Reddy, Shubham Nimkar, Mansi Patel, Sourya Acharya
Jawaharlal Nehru Medical College, Datta Meghe Institute of Medical Sciences (Deemed to be University), Sawangi (Meghe), Wardha, Maharashtra, India

Рубрики: Гастроэнтерология

Разделы: Справочник специалиста

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Резюме

Золотим стандартом для оцінки фіброзу печінки є її біопсія. Однак ця процедура інвазивна і пов’язана з болем, а іноді й зі смертельними наслідками. Точність результатів біопсії печінки ще більше погіршується внаслідок варіабельності результатів в одного та різних дослідників. Використовуються тільки невеликі зразки. Це призводить до змішування двох типів варіабельності, про які говорилося вище. Через ці обмеження були розроблені неінвазивні підходи до скринінгу на фіброз. Різні біохімічні показники сироватки крові або методи візуалізації, що забезпечують фізичне вимірювання жорсткості печінки, дозволяють неінвазивно оцінити фіброз печінки.

The gold standard for assessing liver fibrosis is a liver biopsy. However, the procedure is invasive and is associated with pain and sometimes fatal consequences. The accuracy of liver biopsy results is further harmed by intra- and inter-observer variability. Small samples only. This muddles the two types of observer variability discussed above. Due to these limitations, non-invasive approaches for fibrosis testing have been developed. Various biochemical serum indicators or imaging techniques that provide a physical measure of hepatic stiffness are non-invasive approaches for assessing liver fibrosis.


Ключевые слова

оцінка жорсткості печінки; транзиторна еластографія; магнітно-резонансна еластографія; ФіброТест; хронічні захворювання печінки; хронічний гепатит В; цироз печінки; індекс співвідношення аспартатамінотрансферази до тромбоцитів

liver stiffness assessment; transient elastography; magnetic resonance elastography; FibroTest; chronic liver disease; chronic hepatitis B; cirrhosis; aspartate aminotransferase-to-platelet ratio index

doi: http://dx.doi.org/10.22141/2308-2097.56.4.2022.519

Introduction

The diagnosis of liver injury is a crucial step in the treatment of chronic liver disease (CLD) patients. Liver biopsy is the excellent diagnostic tool for assessing necrosis, inflammation, and fibrosis of the liver, but due to the limitations of an intrusive process and the requirement for repeat sampling, non-invasive tests (NITs) have been developed as an alternative to liver biopsy. Biological (serum biomarkers) and physical (imaging measurement of tissue stiffness) evaluation are commonly used non-invasive tests. However, at present existing NITs have various disadvantages like flexibility, insufficient precision, and error risk factors, while the development of a future generation of fibrosis biomarkers may be hampered by the intrinsic sampling error of reference standard. Most of today’s non-invasive tests were designed to detect fibrosis in chronic hepatitis C patients and finally modified for detecting prognosis in chronic liver disease. These non-invasive tests were not meant to represent the dynamic process of fibrogenesis, differentiate between neighboring disease stages, or diagnose non-alcoholic steatohepatitis, despite their expanding usage in clinical practice. Understanding the benefits and limitations of these non-invasive tests will help clinicians make more informed decisions in the clinic, where non-invasive diagnostics should be used in addition to, not in instead of, liver biopsy. Chronic hepatitis B (CHB) infection is associated with high morbidity and death because it can develop to cirrhosis or hepatocellular carcinoma. It is critical to diagnose liver cirrhosis in CHB patients early to prevent disease progression [1]. There is now an increased availability and greater acceptance of NITs as an alternative to biopsy for diagnosis of advanced fibrosis and determination of prognosis in CLD [2]. Simple serum markers require further validation in patients with CHB and significant fibrosis in inactive or immune tolerant states [3]. Antiviral therapy in CHB results in viral suppression and fibrosis regression, including the reversal of cirrhosis [4–6]. Despite the low cost, ease of interpretation, and access advantages in resource limited settings, simple markers, such as aspartate aminotransferase-to-platelet ratio index (APRI) and Fibrosis-4 score, have limited diagnostic accuracy in moderate-to-severe stages of CHB and do not reflect changes in fibrosis. Patients with insulin resistance and metabolic syndrome, especially manifest type 2 diabetes, should also be screened for the presence of non-alcoholic fatty liver disease (NAFLD) according to the European guidelines, regardless of the level of liver enzymes [7].

Discussion

Serum biomarkers

Fibrosis is a complicated cellular interaction involving inflammatory cytokines and adipokines, as well as angiogenic and neuroendocrine signals, that is regulated by host genetic variables. Co-morbidities in the host, such as alcohol, add to the fibrogenic cascade’s imbalance. Serum biomarkers have the potential to reflect these dynamic changes, allowing for earlier detection of matrix turnover in disease. Direct indicators, which are largely complicated proteins originating from myofibroblasts and extracellular matrix remodeling, and indirect indicators, which are relatively simple biochemical tests that assess disease severity, are being used in clinical biomarker algorithms.
Advantages of biomarkers in chronic liver disease:
1. Provides early diagnosis.
2. High diagnostic accuracy.
3. Tissue specific.
4. Provides prognosis.
5. Not influenced by physiologic variation (for example, due to age, gender, diet, body habitus, exercise, or diurnal variation).
6. Reproducible characteristics across diagnostic platforms.
7. Minimal variation across multi-ethnic populations.

Imaging elastography

The first ultrasound-based elastography, transient elastography, was created and is now a well-established non-invasive method for detecting and staging hepatic fibrosis. The velocity of low frequency elastic shear waves travelling through the liver is measured using a mono-dimensional ultrasound to assess liver stiffness [8–10]. Transient elastography can be completed quickly and has a high intra- and inter-observer variability. A 3.5 MHz ultrasonic transducer is mounted on the axis of a low-amplitude vibrator in the FibroScan® probe (frequency of 50 Hz and amplitude of 2 mm peak-to-peak). The tip of the ultrasonic transducer is placed in the right intercostal area, at the level of the right lobe of the liver, to acquire liver stiffness readings. The vibrator generates an elastic shear wave to the liver when it is activated, while the ultrasound transducer performs a sequence of ultrasonic acquisitions (transmission/reception) with a 4 kHz repeat frequency. Tissue stiffness is measured via elastography. Ultrasound-based elastography only measures a small portion of tissue stiffness when assessing liver fibrosis. Many other factors can impact liver tissue stiffness, they have been found to affect the accuracy of elastography in assessing liver fibrosis and include: inflammation from acute hepatitis, cholestasis from biliary tract blockage, blood congestion due to hepatic outflow obstruction and portal hypertension, and food consumption.
To scan the micron-level displacements associated with mechanical-induced shear wave propagation, magnetic resonance elastography (MRE) uses a modified phase-contrast approach. Quality metrics are established across platforms, unlike in the United States. Cost and availability are limitations, as are patient-specific considerations, such the presence of magnetically sensitive implants, breath-hold compliance, and claustrophobia. Technical failure is also linked to iron overload, a higher body mass index, and severe ascites [11]. Diagnostic MRE fibrosis stage criteria varied between research, and appropriate liver stiffness thresholds derived from meta-analyses of primarily retrospective data, using diverse histologic scoring methods, need to be validated further.
Advantages and disadvantages of serum biomarkers over transient elastography: FibroMeter, FibroTest, and APRI tests, as well as combinations of them, have remarkable inter-laboratory reproducibility. APRI is a low cost, generally available test (being non-patented). However, when it comes to cirrhosis diagnosis, these tests fall short of transient elastography [7]. Furthermore, test results are rarely available right once. The tests aren’t specific for liver disease, and they don’t distinguish between the various phases of fibrosis.

Conclusions

The staging of liver fibrosis is an important element of the clinical management of any type of CLD. Various NITs, when used together, may help guide clinical decision making, minimize the amount of specialization referrals from general care, and eliminate the necessity for invasive biopsy procedures. Current NITs, on the other hand, have significant flaws, including a lack of differentiation between non-alcoholic steatohepatitis and simple steatosis, as well as validation for longitudinal assessment and fibrosis regression following therapeutic therapies (antiviral therapy in viral hepatitis).
 
Received 01.10.2022
Revised 12.10.2022
Accepted 15.10.2022

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